Ubiquinone is a naturally-derived component that is also commonly known as coenzyme Q. Coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-polyprenyl-1,4-benzoquinone in which the number of side-chain isoprene units is 10, and is a ubiquinone peculiar to human beings. This compound is named ubidecarenone in the Japanese pharmacopoeia, coenzyme Q10 as a food additive, and ubiquinone as a cosmetic material.
Ubiquinone is an essential coenzyme for energy production in mitochondria and is an important substance in a living organism as an anti oxidizing substance. It is confirmed that ubiquinone is effective for heart disease, hypertension and rheumatic valve disease, probably because ubiquinone improves cell metabolism. In addition, ubiquinone improves skin roughness and is used in cosmetic agents as described in Patent Document 1.
Ubiquinone has very low water solubility and has high crystallinity. Consequently, formulating ubiquinone is difficult in general. Ubiquinone dissolves well in nonpolar hydrocarbons such as ether and hexane, but shows very low solubility in other solvents. A large number of methods have been proposed for dispersing ubiquinone in a system by using various assistants such as surfactants and clathrating agents. However, these methods have many restrictions on prescription. Further, the obtainable products have low physical stability and long-term storage results in separation or precipitation. Increasing the ubiquinone concentration will be effective for ensuring or improving effects of ubiquinone preparations. However, because of the poor water solubility and high crystallinity, it has been difficult to ensure a sufficient concentration of ubiquinone in an aqueous agent that is the most frequent formulation.
Ubiquinol occurs when ubiquinone is reduced with two hydrogen atoms. This compound is said to be more effective for antioxidation than ubiquinone. Application of ubiquinol in food has been studied. Patent Document 2 discloses ubiquinol-rich fatty food, and Patent Document 3 describes health food containing ubiquinol. Patent Document 4 discloses a dermatological preparation containing ubiquinol.
The water solubility of ubiquinol only slightly surpasses that of ubiquinone. Because of high antioxidant ability, ubiquinol is more unstable to oxidation and is easily oxidized in the air into ubiquinone. The poor water solubility and easy oxidation make formulating ubiquinol more difficult than formulating ubiquinone.
To improve the poor water solubility of ubiquinone, the hydrophilicity of ubiquinone is increased by chemical modification by introducing polar groups. Patent Document 5 discloses a water-soluble ubiquinone prodrug in which ubiquinone is substituted with hydrophilic groups. However, the formulations of hydrophilic ubiquinone have been limited to oral administration and injection administration, and the knowledge of hydrophilic ubiquinone has been very little. There has been no knowledge of transdermal administration of hydrophilic ubiquinone, and the use of ubiquinone as a skin agent for external use has never been anticipated.
The hydrophilic ubiquinone prodrug is expected to produce effects when the polar group-modified ubiquinone is converted by the enzyme activity in the body into antioxidant ubiquinone and ubiquinol.
It has never been anticipated that the hydrophilic ubiquinone derivative itself possesses higher radical scavenging ability than ubiquinone, and prevents skin oxidation, namely skin aging.
Patent Document 1: Japanese Patent Application Laid-Open Publication No. S58-180410
Patent Document 2: WO 2003/061395
Patent Document 3: Japanese Patent Application Laid-Open Publication No. 2006-89422
Patent Document 4: Japanese Patent Application Laid-Open Publication No. 2006-16305
Patent Document 5: WO 96/17626